The long term objectives of our research are the establishment and elucidation of the role of histamine (Hist) or a related imidazole- containing compound, in neurotransmission in acousticolateralis organs especially the semicircular canal (SCC). Specifically, the establishment of Hist's role requires fulfillment of several criteria including those of synthesis, presence and release. Whether the criterion of presence is fulfilled or not will be tested by the use of immunocytochemical techniques designed to detect histamine. Some evidence for the presence of the synthesizing enzyme histidine decarboxylase in the SCC has already been recorded. The fulfillment of the release criterion will be tested by stimulating the isolated SCC electrically and determining the presence of Hist (or congeners) by high performance liquid chromatography. The H1 and H2 antagonists have previously been shown to suppress afferent firing in the SCC. A role for Hist in neurotransmission in the SCC may also underlie the still-enigmatic finding that reserpine and other amine-depleting drugs cause a loss of electron-opacity in the synaptic bodies of vestibular hair cells. According to most authorities neither catecholamines nor indolamines are involved in hair cell recepto-neural transmission. Less well-known that the ability of reserpine to release and deplete catecholamines nor indolamines is its ability to release and deplete Hist. It is therefore proposed that we investigate whether the electron opacity of the synaptic body may be due to Hist storage. This will be done in two ways: 1) by collecting the fluid bathing the SCC following reserpine treatment and analyzing it for Hist and cogeners and 2) by determining whether repletion f electron opacity is hastened by treatment with the Hist precursor histidine. This research may provide evidence for the role of the synaptic body in hair cell receptoneural transmission; the role of Hist in hair cell transmission and finally provide a definite mechanism for the well-known suppressive effect of antihistamines in vestibular disorders.